Deletion patterns of the STS gene and flanking sequences in Israeli X-linked ichthyosis patients and carriers: analysis by polymerase chain reaction and fluorescence in situ hybridization techniques

Background Deletion of the entire steroid sulfatase (STS) gene is the most common molecular defect in X-linked ichthyosis (XLI) patients. Usually, add itional flanking sequences are also missing. The aim of this study was to e stimate the extent of deletions in an ethnically heterogeneous population o f Israeli XLI patients. Methods Multiplex polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH) techniques were applied in the analysis of blood sampl es of 24 patients and amniotic cells of seven affected fetuses from 22 unre lated families. Results In 19 families, a large deletion of the 2-3 megabase was found. It included the whole STS gene and spanned adjacent areas up- and downstream b etween the loci DXS 1139 and DXS 1132. Two unrelated families of Iraqi ance stry had a partial deletion of the gene and its centromeric adjacent sequen ce. In another family, the telomeric end of the extragenic segment was only partially missing. Application of FISH on metaphase blood cells and interp hase amniotic cells confirmed the diagnosis of XLI in all patients, except the three with partial intragenic deletion. In those cases, the remaining f raction of the gene was sufficient to provide a false negative result. Diag nosis of carriers and prenatal diagnosis in uncultured cells was applicable only by FISH. Conclusions Our study revealed a remarkable heterogeneity in the deletion p attern among Israeli patients with XLI. This heterogeneity could not be att ributed to specific ethnic groups because of the small size of the study gr oup. More studies involving patients of various ancestries should be carrie d out. In addition, this study demonstrated the usefulness of the FISH tech nique in the prenatal diagnosis of fetuses with suspected XLI.